Humans may sometimes suffer fear or aversive experiences in ordinary human relationships or social life or on account of extraordinary accidents, natural disasters, and the like. An event that has caused a serious effect on the survival of an individual or the environment in which the individual has suffered the effect is encoded as “fear memory” in the cranial nerve circuit; in order for the individual to secure behavioral flexibility, this circuit has to be modified or reconstructed as controlled by experience or time. In humans, a failure of this modification or reconstruction is held to be involved in so-called anxiety associated disorders (Non-Patent Document 1.) Anxiety associated disorders are diseases that cause great pain in the patient and are commonly found in people's ordinary life. According to a large-scale epidemiological study made in the United States of America, the lifetime prevalence of mental diseases is as high as 46% (Non-Patent Document 2), of which 29% is occupied by anxiety associated disorders. A survey involving the general Dutch population found that the odds at which people bear a suicide ideation within three years is 2.3 times as high when they have an anxiety disorder as when they have no anxiety associated disorder, even after adjustment of mental illness other than anxiety disorder as well as social factors such as occupation and marital history, and the figure increases to 3.6 in the case of suicide attempt (Non-Patent Document 3.) In Japan, too, more than 30,000 people have committed suicide annually for the past ten years (Non-Patent Document 4.) Thus, carrying out studies on anxiety associated disorders may well be considered to be one of the most important topics in the discipline of psychiatry.
An intense fear memory that is inflicted on the mind by fear or aversive experience can potentially evoke traumatic memory (trauma.) A disorder in certain social function or mental function may derive from such traumatic memory and it can hamper an individual's social life to pose a problem. Posttraumatic stress disorder (PTSD) is a disease characterized by the occurrence of various stress disorders on account of traumatic memory from having experienced a shocking event and there are diverse possible causes, including disasters such as earthquakes, floods and fires, or manmade disasters such as accidents and wars, as well as crimes such as terrorism and physical abuse. PTSD has characteristic features including persistent symptoms of increased arousal (Non-Patent Document 5.) According to a survey of the World Health Organization, 1.1 to 1.6% of the Japanese population suffer PTSD in their lifetime and the incidence tends to rise in their twenties to early thirties, frequently accompanied by anxiety disorder and depressive state, or addictive diseases such as alcohol or drug abuse, as well as eating disorders. While non-drug therapies such as cognitive behavioral therapy are currently practiced as methods to treat PTSD, a study is being made to evaluate the efficacy of a drug therapy using a selective serotonin re-uptake inhibitor (SSRI) (Non-Patent Document 6.)
The amygdala and the hippocampus which are brain areas are considered to play a major role in the formation of trauma-evoking memory of a fearful experience or an aversive experience (Non-Patent Document 7.) It has been reported that in the hippocampus, neurogenesis is taking place even in mature animals and that neurogenesis is involved in long-term changes in the nature of fear and aversive memories (Non-Patent Document 8.)
Polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and arachidonic acid (AA) have been reported to exhibit an action for modifying the neurogenesis in the hippocampus (Non-Patent Documents 9 to 11) and as regards the amygdala and the hippocampus, it has been further reported that fatty acid derivatives such as endocannabinoid function as a nerve transmission modifier (Non-Patent Document 12.) A report has also been published that the modification of cannabinoid's functions affects the memories of fear and aversion (Non-Patent Document 13.)
A report has been made of the use of n-3 polyunsaturated fatty acids such as docosahexaenoic acid, eicosapentaenoic acid, and α-linolenic acid for the purpose of preventing or treating senile dementia (Patent Documents 1 to 3.) A report has also been made of arachidonic acid intended for preventing or improving the lowering of brain functions (Patent Documents 4 and 5.)
It has recently been reported that in an experiment where obese rats (Zucker rats) were kept on a feed mixed with krill oil, the DHA in the brain's phospholipids increased significantly (Non-Patent Document 14.) Heretofore, several reports have been made of experiments using fish oil containing EPA and DHA. Hamasaki et al. reported that upon ingesting DHA-rich fish oil capsules, the aggressiveness of university students was lowered in comparison with a control group (Non-Patent Document 15.) Recently, Matsuoka et al. reported that the ingestion of DHA/EPA capsules had a preventive effect on the development of PTSD (Non-Patent Document 16.) Further, Waku reported that the cannabinoid receptor is closely involved in higher brain functions and that substances acting on the cannabinoid receptor can potentially be applied in therapeutics for obesity, pain, and other conditions (Non-Patent Document No. 17.)